Abstract
Annual Review of Pharmacology and Toxicology
Vol. 47:
443-467
(Volume publication date February 2007)
(doi:10.1146/annurev.pharmtox.47.120505.105359)
First published online as a Review in Advance on August 29, 2006mTOR Pathway as a Target in Tissue Hypertrophy Chung-Han Lee,1,2 Ken Inoki,1,2 andKun-Liang Guan1,2,31Life Science Institute, 2Department of Biological Chemistry, and 3Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109; email: chunghl@umich.edu, keninoki@umich.edu, kunliang@umich.edu Abstract Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an integral cell growth regulator. The mTOR pathway involves two functional complexes, TORC1 and TORC2, which have been defined by both their association with raptor or rictor, respectively, and their sensitivity to short-term rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size. As a result, both physiologic and pathologic tissue hypertrophy are associated with TORC1 activation. Some clinical examples include skeletal and cardiac muscle hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy. Clarification of the mTOR pathway may lead to increased understanding of both the etiology and consequences of aberrant cell size regulation. This review covers some of the biochemical regulation of the mTOR pathway that may be important to the regulation of cell size, and it will present several potential clinical applications where the control of cell size may be biologically significant. Evaluation of the mammalian target of rapamycin pathway and the effect of rapamycin on target expression and cellular proliferation in osteosarcoma cells from dogs American Journal of Veterinary Research 69(8):1079-1084 (2008) Crystal structure of the yeast eIF4A-eIF4G complex: An RNA-helicase controlled by protein-protein interactions Proceedings of the National Academy of Sciences 105(28):9564-9569 (2008) Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice Proceedings of the National Academy of Sciences 105(6):2022-2027 (2008) Pulmonary lymphangioleiomyomatosis (LAM): Progress and current challenges Journal of Cellular Biochemistry 103(2):369-382 (2008) Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53 The EMBO Journal 26(23):4812-4823 (2007)
|
|
|
Users who read this review also read:
| Mondira Kundu, Craig B. Thompson Annual Review of Pathology: Mechanisms of Disease. Volume 3, Page 427-455, Feb 2008 Abstract
| Full Text
| PDF (332 KB)
|
Add to Favorites
| Related | |
| Sten Orrenius, Vladimir Gogvadze, Boris Zhivotovsky Annual Review of Pharmacology and Toxicology. Volume 47, Page 143-183, Feb 2007 Abstract
| Full Text
| PDF (379 KB)
|
Add to Favorites
| Related | |
| Makoto R. Hara, Solomon H. Snyder Annual Review of Pharmacology and Toxicology. Volume 47, Page 117-141, Feb 2007 Abstract
| Full Text
| PDF (1668 KB)
|
Add to Favorites
| Related | |
| Lauren T. May, Katie Leach, Patrick M. Sexton, Arthur Christopoulos Annual Review of Pharmacology and Toxicology. Volume 47, Page 1-51, Feb 2007 Abstract
| Full Text
| PDF (552 KB)
|
Add to Favorites
| Related | |
|
|